1. Field of the Invention
The present invention relates to utilize NiSOD-like compound and derivatives thereof as a pharmaceutical composition. More specifically, NiSOD-like compound and derivatives thereof are used for suppressing abnormal protein aggregation, recovering cell viability, increasing mature neuron number and neurite outgrowth length and protecting dopaminergic cells by reducing oxidative stress or reactive oxygen species in brain tissues.
2. Description of the Prior Art
As the elderly population of the world continues to increase, the prevalence of neurodegenerative disorders, such as spinocerebellar ataxia (SCA), Alzheimer's disease (AD) and Parkinson's disease (PD), has been increasing at a disconcerting rate. Despite tremendous progress that has made in neurodegenerative disorders research in the past few decades, there is still no effective treatment for such diseases.
Neurodegeneration is an umbrella term for the progressive loss of structure or function of neurons, including death of neurons. As research progresses, many similarities appear that are related these diseases to one another on a cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death; moreover, with age, the risk of DNA mutation increases, as well as the risk of cell damage induced by oxidative stress.
Although SCA, AD and PD manifest with different clinical features, the disease processes at the cellular level appear to be similar.
In SCA disease, the expansions of CAG repeats in the disease genes result in long polyglutamine (polyQ) tracts in the respective proteins. The accumulation of intranuclear and cytoplasmic misfolded polyQ proteins is thought to induce oxidative stress and lead to cell death. Patients with SCA find that their ability to use the affected parts of the body becomes progressively more difficult and less exact.
AD has been categorized to be a protein misfolding disease, caused by accumulation of abnormally folded A-beta and tau proteins in the brain, which leads to progressive loss of memory. A-beta protein is made up of small peptides, 39-43 amino acids in length, called beta-amyloid (also written as Aβ oligomer). Aβ oligomer is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP is critical to neuron growth, survival and post-injury repair.
PD is a neurodegenerative movement disorder. In most cases it occurs as a sporadic type of disease, but there are also rare familial forms. Pathologically Parkinson's disease is characterized by loss of dopaminergic neurons in the compact part of substantia nigra. As a part of the neurodegenerative process protein aggregates will accumulate as Lewy bodies in dopaminergic neurons. In PD, research on protein misfolding and aggregation has taken center stage following the association of alpha-synuclein gene mutations with familial forms of the disease.
The above protein aggregation leads to the increase of oxidative stress which has been implicated as a factor for the initiation and progression of neurodegenerative disorders. Thus, suppression of the protein aggregation and reduction of oxidative stress in the neurodegenerative disorders are expected to inhibit a wide range of harmful downstream events and further provide an observation for identifying the potential prevention and treatment of neurodegenerative disorders.